Process and apparatus for the throughflow sterilization of liquids

ABSTRACT

The invention relates to an apparatus and a process for the throughflow sterilization of biologically contaminated liquids.

The invention relates to an apparatus and a process for the throughflowsterilization of biologically contaminated liquids.

It is highly undesirable for bacteria to become established or to spreadon the surfaces of pipelines, or of containers or packaging. Slimelayers frequently form and permit sharp rises in microbial populations,and these can lead to persistent impairment of the quality of water orof drinks or foods, and even to spoilage of the product, and harm to thehealth of consumers.

Bacteria must be kept away from all fields of life where hygiene isimportant. This affects textiles for direct body contact, especially inthe genital area, and those used for the care of the elderly or sick.Bacteria must also be kept away from the surface of the furniture and ofinstruments in patient-care areas, especially in areas for intensivecare or neonatal care, and in hospitals, especially in areas wheremedical intervention takes place, and also in isolation wards forcritical cases of infection, and in toilets.

A current method of treating equipment, or the surfaces of furniture orof textiles, to resist bacteria either when this becomes necessary orelse as a precautionary measure is to use chemicals or solutions ofthese, or else mixtures, these being disinfectant and having fairlybroad general antimicrobial action. Chemical agents of this type actnonspecifically and are themselves frequently toxic or irritant, or formdegradation products which are hazardous to health. In addition, peoplefrequently exhibit intolerance to these materials once they have becomesensitized.

Another procedure for counteracting surface spread of bacteria is theincorporation of antimicrobial substances into a matrix.

Another challenge of constantly increasing significance is the avoidanceof algal growth on surfaces, since there are many external surfaces ofbuildings with plastic cladding, which is particularly susceptible tocolonization by algae. As well as giving an undesirable appearance, thiscan in some circumstances also impair the functioning of the componentsconcerned. One relevant example is colonization by algae of surfaceswith a photovoltaic function.

Another form of microbial pollution for which again no technicallysatisfactory solution has been found is fungal infestation of surfaces.For example, Aspergillus niger infestation of joints or walls in wetareas within buildings not only impairs appearance but also has serioushealth implications, since many people are allergic to the substancesgiven off by the fungi, and the result can even be serious, chronicrespiratory disease.

In the marine sector, the fouling of boats' hulls affects costs, sincethe growth of fouling organisms is attended by an increase in the boat'sflow resistance, and thus by a marked increase in fuel consumption.Problems of this type have hitherto generally been countered byincorporating toxic heavy metals or other low-molecular-weight biocidesinto antifouling coatings, with the aim of mitigating the problemsdescribed. To this end, the damaging side effects of coatings of thistype are accepted, but as society's environmental awareness rises, thisstate of affairs is increasingly problematic.

U.S. Pat. No. 4,532,269, for example, therefore discloses a terpolymermade from butyl methacrylate, tributyltin methacrylate, andtert-butylaminoethyl methacrylate. This copolymer is used as anantimicrobial paint for ships, and the hydrophilic tert-butylaminoethylmethacrylate promotes slow erosion of the polymer, thus releasing thehighly toxic tributyltin methacrylate as active antimicrobial agent.

In these applications, the copolymer prepared with aminomethacrylates ismerely a matrix or carrier for added microbicidal active ingredientswhich can diffuse or migrate out of the carrier material. At some stagepolymers of this type lose their activity, once the necessary minimuminhibitor concentration (MIC) at the surface has been lost.

It is also known from the European patent application 0 862 858 thatcopolymers of tert-butylaminoethyl methacrylate, which is a methacrylatewith a secondary amino function, have inherent microbicidal properties.

The use of antimicrobial polymers for the disinfection of liquids istherefore known.

Nevertheless, the sterilization of water systems and of ultra highpurity-water systems represents a major challenge. The requirementsplaced upon sterilization processes of this type are very stringent,especially in those fields which can give rise to a direct source ofcontamination for humans, e.g. in the field of pharmaceuticalproduction, or of the processing of drinking water or of other drinks orfoods. It is specifically in fields of this type that cold sterilizationmethods are desirable, since the solutions processed here also comprisetemperature-sensitive products. In addition, the amount of energyconsumed by sterilization should be as small as possible. UVdisinfection systems can only be used for UV-resistant solutions, i.e.not for food or drinks production. Low-molecular-weight biocides cannotby their very nature generally be used for purposes of this type, sincethese agents can have considerable potential for human toxicity.

Another problem not yet satisfactorily solved is the production ofdrinking water in developing countries. Plants for this purpose shouldrequire little maintenance, be simple to produce, consume little energy,and be highly efficient.

The object on which the present invention is based is therefore todevelop a process which does not have the disadvantages described of theprior art for the cold-sterilization of liquids, such as water.

It has been found that throughflow systems which comprise a fillingcoated with antimicrobial polymers comply with the requirements profiledescribed in an almost ideal manner.

The present invention therefore provides an apparatus for sterilizingliquids, composed of a hollow body which has been filled entirely orpartly with a filling or with internals, and through which the liquidflows, wherein the filling or the internals comprise antimicrobialpolymers.

The apparatus of the invention may also have an electrical or mechanicalpump which can pump the liquid to be sterilized through the apparatus.The liquid may also flow under its own pressure through the apparatus,from a reservoir located above the apparatus.

The location of the filling in the apparatus of the invention isadvantageously in a tube or in a closed throughflow cartridge. It is notessential that the filling occupies the entire cavity available, but forefficient sterilization the available surface area with theantimicrobial polymers should be as large as possible.

The filling or the internals may have been prefabricated and may becomposed of glass, polymers, metals, or ceramics, for example, orcomprise these materials.

For the purposes of the present invention, examples of a filling orinternals are: Raschig rings, saddles, Pall rings, tellerettes, wiremesh rings, or wire mesh fabrics. Examples of internals are filterplates, baffles, column trays, and perforated plates. For the purposesof the present invention, possible internals include two or more narrowtubes installed in parallel giving something of the nature of amultitube reactor. Particular preference is given to structured mixerpackings or demister packings. These fillings or internals are thensubsequently coated with the antimicrobial polymers.

The coating of the filling here may take place directly using a solutionof the at least one antimicrobial polymer in a, generally organic,solvent, or using an aqueous dispersion of the antimicrobial polymer.

Solvents which may be used for the coating formulation are almost any ofthe organic solvents which dissolve the antimicrobial polymer at anadequate concentration. Examples of these include alcohols, esters,ketones, aldehydes, ethers, acetates, aromatics, hydrocarbons,halogenated hydrocarbons, and organic acids, in particular methanol,ethanol, propanol, butanol, acetone, methyl ethyl ketone, butyl acetate,acetaldehyde, ethylene glycol, propylene glycol, THF, diethyl ether,dioxane, toluene, n-hexane, cyclohexane, cyclohexanol, xylene, DMF,acetic acid, and chloroform.

In another version of the process, at least one antimicrobial polymermay be incorporated into a lacquer which is used for the coating of thefilling or internals. The antimicrobial polymers may also be applied tothe filling by melting or other thermal forming processes. In particularcases it is also possible for the filling used to be the antimicrobialpolymers as they stand, particularly in pelletized form.

It is also possible to use a polymer blend made from antimicrobial andnon-antimicrobial polymers to produce the filling or the antimicrobialcoatings. Examples of non-antimicrobial polymers are polymethylmethacrylate, PVC, polyacrylic acid, polystyrene, polyolefins,polyterephthalates, polyamides, polysulfones, polyacrylonitrile,polycarbonates, polyurethane, and cellulose derivatives.

The antimicrobial polymers are preferably prepared from nitrogen- orphosphorus-functionalized monomers. Particularly suitable antimicrobialpolymers for this purpose are those prepared from at least one monomerselected from the group consisting of

2-tert-butylaminoethyl methacrylate, 2-diethylaminoethyl methacrylate,2-diethylaminomethyl methacrylate, 2-tert-butylaminoethyl acrylate,3-dimethylaminopropyl acrylate, 2-diethylaminoethyl acrylate,2-dimethylaminoethyl acrylate, dimethylaminopropylmethacrylamide,diethylaminopropylmethacrylamide, N-3-dimethylaminopropylacrylamide,2-methacryloyloxyethyltrimethylammonium methosulfate,2-diethylaminoethyl methacrylate,2-methacryloyloxyethyltrimethylammonium chloride,3-methacryloylaminopropyltrimethylammonium chloride,2-methacryloyloxyethyltrimethylammonium chloride,2-acryloyloxyethyl-4-benzoyidimethylammonium bromide,2-methacryloyloxyethyl-4-benzoyldimethylammonium bromide,allyltriphenylphosphonium bromide, allyltriphenylphosphonium chloride,2-acrylamido-2-methyl-1-propanesulfonic acid, 2-diethylaminoethyl vinylether, and 3-aminopropyl vinyl ether.

Besides the monomers mentioned, other aliphatically unsaturated monomersmay be used in preparing the antimicrobial polymers. It is not essentialthat the other aliphatically unsaturated monomers, too, have additionalantimicrobial action. Suitable monomers are acrylic or methacryliccompounds, e.g. acrylic acid, tert-butyl methacrylate, or methylmethacrylate, or styrene or its derivatives, vinyl chloride, vinylethers, acrylamides, acrylonitriles, olefins (ethylene, propylene,butylene, isobutylene), allyl compounds, vinyl ketones, vinylaceticacid, vinyl acetate, vinyl esters, methyl methacrylate, ethylmethacrylate, butyl methacrylate, tert-butyl methacrylate, methylacrylate, ethyl acrylate, butyl acrylate, and/or tert-butyl acrylate.

The apparatuses of the invention are suitable for sterilizing any of theliquids in which undesirable bacteria can be present. Examples of theseare drinking water, process water in the chemical or pharmaceuticalindustry, or in industries which process food or drink. The apparatusesof the invention may also be used to sterilize bathing water for mobileshowering or washing equipment or swimming pools, or else well water forprivate use. In the food and drink sector it is possible to sterilizeliquid foods or drinks, such as beer, wine, milk, mayonnaise, cremes,ketchup, or soft ice cream, in each case in the form of a final productor of precursors.

The present invention also therefore provides a process for sterilizingliquids comprising water, where the liquid is passed through at leastone of the abovementioned apparatuses, for sterilization.

Examples of liquids which may be sterilized using the apparatus of theinvention or the process of the invention are the abovementionedliquids, drinking water, waste water, process water, and food or drinkin liquid or paste form, where these can be pumped through appropriateapparatuses.

The examples below are given for further description of the presentinvention and provide additional illustration of the invention but donot restrict its scope as set out in the patent claims.

EXAMPLE 1

50 ml of tert-butylaminoethyl methacrylate (Aldrich) and 240 ml ofethanol are charged to a three-necked flask and heated to 65° C. under astream of argon. 0.4 g of azobisisobutyronitrile dissolved in 15 ml ofethanol are then slowly added dropwise, with stirring. The mixture isheated to 70° C. and stirred at this temperature for 6 hours. Afterexpiry of this time, the solvent is removed by distillation from thereaction mixture. The product is then dried in vacuo at 50° C. for 24hours. The reaction product is then finely ground in a mortar.

EXAMPLE 1a

1 g of the product from example 1 is dissolved in one liter ofcyclohexane. 1000 glass rings of length 7 mm and internal diameter 5 mm,divided into portions of 100 glass rings each, are dipped into thissolution, in each case for 10 seconds. The glass rings are then removedand dried for 24 hours at 40° C. in a drying cabinet. The resultantpredried coating is then further dried at about 1 mbar in a vacuumdrying cabinet at 35° C. for 24 hours. The dried glass rings are placedin a glass tube of length 1 m and diameter 8 cm, both openings of whichare sealed with glass wool, and the lower outflow of which has a valveto regulate throughflow.

EXAMPLE 1b

The glass tubes from example 1a are clamped vertically into a stand, andone liter of a microbial suspension of Staphylococcus aureus which has107 microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. No remaining Staphylococcus aureus microbes are detectable.

EXAMPLE 1c

The glass tubes from example 1a are clamped vertically into a stand, andone liter of a microbial suspension of Pseudomonas aeruginosa which has107 microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. The number of microbes has fallen to 10³ microbes per ml.

EXAMPLE 2

40 ml of dimethylaminopropylmethacrylamide (Aldrich) and 200 ml ofethanol are charged to a three-necked flask and heated to 65° C. under astream of argon. 0.4 g of azobisisobutyronitrile dissolved in 20 ml ofethanol are then slowly added dropwise, with stirring. The mixture isheated to 70° C. and stirred at this temperature for 6 hours. Afterexpiry of this time, the solvent is removed by distillation from thereaction mixture and the product is then dried in vacuo at 50° C. for 24hours. The reaction product is then finely ground in a mortar.

EXAMPLE 2a

1 g of the product from example 2 is dissolved in one liter ofcyclohexane. 1000 glass rings of length 7 mm and internal diameter 5 mm,divided into portions of 100 glass rings each, are dipped into thissolution, in each case for 10 seconds. The glass rings are then removedand dried for 24 hours at 40° C. in a drying cabinet. The resultantpredried coating is then further dried at about 1 mbar in a vacuumdrying cabinet at 35° C. for 24 hours. The dried glass rings are placedin a glass tube of length 1 m and diameter 8 cm, both openings of whichare sealed with glass wool, and the lower outflow of which has a valveto regulate throughflow.

EXAMPLE 2b

The glass tubes from example 2a are clamped vertically into a stand, andone liter of a microbial suspension of Staphylococcus aureus which has107 microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. The number of microbes has fallen to 103 microbes per ml.

EXAMPLE 2c

The glass tubes from example 2a are clamped vertically into a stand, andone liter of a microbial suspension of Pseudomonas aeruginosa which has10⁷ microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. The number of microbes has fallen to 1 microbes per ml.

EXAMPLE 3

16 ml of tert-butylaminoethyl methacrylate (Aldrich), 45 g of Triton X405 (Aldrich), 200 ml of deionized water, and 0.6 g of potassiumperoxodisulfate (Aldrich) are charged to a three-necked flask and heatedto 60° C. under a stream of argon. A further 180 ml oftert-butylaminoethyl methacrylate are then slowly added dropwise over aperiod of 4 hours. The mixture is then stirred for a further 2 hours at60° C., and then the resultant emulsion is allowed to cool to roomtemperature.

EXAMPLE 3a

5 g of the product from example 3 is diluted in one liter of water. 1000glass rings of length 7 mm and internal diameter 5 mm, divided intoportions of 100 glass rings each, are dipped into this dispersion, ineach case for 10 seconds. The glass rings are then removed and dried for24 hours at 40° C. in a drying cabinet. The resultant predried coatingis then further dried at about 1 mbar in a vacuum drying cabinet at 35°C. for 24 hours.

The dried glass rings are placed in a glass tube of length 1 m anddiameter 8 cm, both openings of which are sealed with glass wool, andthe lower outflow of which has a valve to regulate throughflow.

EXAMPLE 3b

The glass tubes from example 3a are clamped vertically into a stand, andone liter of a microbial suspension of Staphylococcus aureus which has10⁷ microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. The number of microbes has fallen to 10³ microbes per ml.

EXAMPLE 3c

The glass tubes from example 3a are clamped vertically into a stand, andone liter of a microbial suspension of Pseudomonas aeruginosa which has10⁷ microbes per ml is added from above. A throughflow of about 50 mlper minute is set by adjusting the outflow valve. Once all of themicrobial suspension has passed through, the number of microbes is againmeasured. The number of microbes has fallen to 103 microbes per ml.

1. An apparatus for sterilizing liquids, which comprises: a hollow bodywhich has been filled entirely or partly with a filling or withinternals, and through which the liquid flows, wherein the filling orthe internals comprise antimicrobial polymers.
 2. The apparatus asclaimed in claim 1, wherein the filling or the internals have beencoated with antimicrobial polymers.
 3. The apparatus as claimed in claim1, wherein the filling or the internals are composed of a polymer blendmade from antimicrobial and non-antimicrobial polymers.
 4. The apparatusas claimed in claim 1, wherein the antimicrobial polymers are preparedfrom nitrogen- or phosphorus-functionalized monomers.
 5. The apparatusas claimed in claim 1, wherein the antimicrobial polymers are preparedfrom at least one monomer selected from the group consisting of2-tert-butylaminoethyl methacrylate, 2-diethylaminoethyl methacrylate,2-diethylaminomethyl methacrylate, 2-tert-butylaminoethyl acrylate,3-dimethylaminopropyl acrylate, 2—diethylaminoethyl acrylate,2-dimethylaminoethyl acrylate, dimethylaminopropylmethacrylamide,diethylaminopropylmethacrylamide, N-3-dimethylaminopropylacrylamide,2-methacryloyl-oxyethyltrimethylammonium methosulfate,2-diethylominoethyl methacrylate,2-methacryloyloxyethyltrimethylammonium chloride,3-methacryloylaminopropyltrimethyl-ammonium chloride,2-methacryloyloxyethyltrimethylammonium chloride,2-acryloyloxyethyl-4-benzoyldimethylammonium bromide,2-methacryloyloxyethyl-4-benzoyldimethylammonium bromide,allyltriphenylphosphonium bromide, allyltriphenylphosphonium chloride,2-acrylamido-2-methyl-1-propanesulfonic acid, 2-diethylaminoethyl vinylether, and 3-aminopropyl vinyl ether.
 6. The apparatus as claimed inclaim 5, wherein the antimicrobial polymers are also prepared usinganother aliphatically unsaturated monomer.
 7. The apparatus as claimedin claim 1, wherein the filling or the internals comprise glass,polymers, metals, or ceramics.
 8. A process for sterilizing liquidscomprising water, which comprises passing the liquid through at leastone apparatus as claimed in claim 1, for sterilization.
 9. The processas claimed in claim 8, wherein the liquid comprising water is drinkingwater, waste water, process water, or food or drink in liquid or pasteform.